B6.129X1-Bax^tm1Sjk/J

Stock number: 002994
Product name: Bax^-
Research areas: Apoptosis Research, Cancer Research, Developmental Biology Research, Immunology, Inflammation and Autoimmunity Research, Reproductive Biology Research

Description

Homozygous Bax^tm1Sjk mice display aberrant apoptosis with hyperplasia displayed in various tissues, including thymocytes, B cells, and cells of the reproductive organs.

Detailed description

Mice homozygous for the Bax^tm1Sjk mutation are viable but display lineage-specific aberrations in cell death. Thymocytes and B cells from homozygous mutant mice display hyperplasia. Ovaries contain unusual atretic follicles with excess granulosa cells while Bax-deficient males are infertile. There is an accumulation of atypical premeiotic germ cells and no mature haploid sperm found in seminiferous tubules. Multinucleated giant cells and dysplastic cells accompany massive cell death.

Used in conjunction with strain B6.129-Bak1^tm1Thsn/J (see Stock No. 004183), to generate the double knock-out Bak/Bax, a model for demonstrating severe defects in the regulation of apoptosis during development and tissue homeostasis.

Coat color of Bax^tm1Sjk mice
The coat color loci tyrosinase (Tyr) and pink-eyed dilution (p) are linked to the Bcl2-associated X protein (Bax) gene. According to backcross data from the Mouse Genome Database, Bax is at 23.00 cM, p is at 28.00 cM, and Tyr is at 44.00 cM on chromosome 7. The targeted disruption of the Bax gene was performed in a 129-derived RW-4 ES cell line (A^w/A^w p Tyr^c-ch/p Tyr^c) and was backcrossed 8 generations to C57BL/6 (a/a +^p +^Tyr-c/+^p +^Tyr-c; nonagouti black) before arriving at The Jackson Laboratory. The Jackson Laboratory's live colony of B6.129X1-Bax^tm1Sjk/J mice (June 2019) is no longer segregating at the Tyr locus and do not retain the p allele from the 129 ES cell line: coat and eye color is black. However, the mice that were the source of the cryopreserved sperm (cryopreserved in 2003 at N12) may have been segregating at the Tyr locus and might retain the p allele from the 129 ES cell line. Thus, matings of Bax heterozygous (+/-) mice recovered from the cryorepository stock (N12 cryopreserved sperm) may produce progeny of varying coat color including black, white, chinchilla, light chinchilla, or grey, with all but the black mice having pink eyes. Because the potential for crossover between the p and Bax loci is small (roughly 5%), progeny from cryorecovered stock that are grey in color and have pink eyes most likely are homozygous for the targeted Bax gene (-/-).

Development

A Bax targeting vector substituted PGK-Neo for exons 2 through 5, deleting BH1 and BH2 and the capacity for a functional protein. This construct was was electroporated into 129-derived RW-4 ES cell line (A^w/A^w p Tyr^c-ch/p Tyr^c). The resulting chimeric animals were tested for germline transmission. The mice were then backcrossed 8 generations to C57BL/6 (a/a +^p +^Tyr-c/+^p +^Tyr-c; nonagouti black) before arriving at The Jackson Laboratory. Upon arrival at The Jackson Laboratory, the mice were crossed to C57BL/6J (Stock No. 000664) at least once to establish the colony.

Allele

Symbol: Bax^tm1Sjk
Name: targeted mutation 1, Stanley J Korsmeyer
MGI accession ID: MGI:1857429
Generation method: Targeted
Attributes: Null/Knockout
Synonyms: Bax^-; Bax1
Marker symbol: Bax
Marker name: BCL2-associated X protein
Marker synonyms: BCL2L4
Chromosome: 7
Strain of origin: 129X1/SvJ
Molecular note: A neomycin selection cassette replaced exons 2 through 4 and part of exon 5, which encode sequences that correspond to the two BCL2 homology domains BH1 and BH2. Immunoblots did not detect the endcoded protein in tissue lysates derived from homozygous mice.